It has long been established that development of conformational structure is dependent on amino acid sequence, although the exact relationship (which would make possible the precise prediction of native conformation from primary structure) remains unclear. It has long been believed that native conformation develops from the randomly coiled chain of the denatured (or newly synthesized) protein, by a process of "nucleation" which would involve a progressive folding, governed by thermodynamic factors, until the native state is reached. This hypothesis rests on the assumption that the denatured protein exists predominantly as a random coil. However it has recently been observed in this and other laboratories that lysozyme, denatured by reduction, contains secondary structure in amounts easily detectable by circular dichroism. This observation has now been extended to other proteins, which are: chymotrypsin, cytochrome c, papain, elastase, staphylococcal nuclease, and ribonuclease. In general their 'denatured' structures are characterized by lowered alpha-helix and either constant or increasing beta structure. Thus, there appears to be a more complex folding mechanism than would be suggested by a process of nucleation. The sequence of events from the 'denatured' structure to the native conformation will be examined to shed more light on the folding mechanism. BIBLIOGRAPHIC REFERENCE: White, F. H., Jr.: Studies on secondary structure in chicken egg-white lysozyme after reductive cleavage of disulfide bonds. Biochemistry 15: 2906-2912, 1976.